The present invention refers to 2-bromomethyl-6-methyl-benzoic acid (I) and a process for the preparation thereof. Compound (I) is a useful intermediate for the synthesis of several products of medicinal interest, such as prostaglandins, antitumour agents and peroxisome proliferator-activated receptor ligands. 
Derivatives of 2,6-dimethyl-benzoic acid (II) are useful building blocks for the synthesis of several products of medicinal interest. 
Among them, 2-bromomethyl-6-methyl-benzoic acid methyl ester (IIIa), used for the preparation of peroxisome proliferator-activated receptor (PPAR) ligands, can be mentioned. 
2-Bromomethyl-6-methyl-benzoic acid methyl ester is usually synthesised by bromination of 2,6-dimethyl-benzoic acid methyl ester (IVa), as reported in literature [WO064888, WO064876, Chem. Ber. (1777), 110(4), 1403-20 and DE 2442069]. 
The reaction disclosed in WO064876 is carried out in carbon tetrachloride and the reagents are N-bromo-succinimide and benzoyl peroxide. Despite purification by flash chromatography, the product is obtained with 85% purity, the remainder being unreacted 2,6-dimethyl-benzoic acid methyl ester.
Another drawback of this method is that if the desired final product contains the carboxylate in the free form or an ester other than the methyl one, 2-bromomethyl-6-methyl-benzoic acid methyl ester (IIIa) must undergo hydrolysis and/or esterification. This problem can be better understood when considering the synthesis of 7-methyl-3H-isobenzofuranone (V), which is also present in compounds of biological interest. 
Compound (V) is synthesised by reduction of 3-methyl-phthalic acid anhydride with sodium borohydride, L-Selectride and lithium trialkyl borohydride. A convenient alternative route would be represented by the ring-closure of compound (I).
It would be therefore useful to provide a method that allows the bromination of 2,6-dimethyl benzoic acid and that affords 2-bromomethyl-6-methyl-benzoic acid (I) in high yield and purity.
The benzylic bromination usually occurs using a bromine source such as N-bromo-hydantoine and N-bromo-succinimide, in the presence of a catalyst and light either at room or higher temperature.
These conditions allow very low selectivity towards monobrominated compounds. In fact, the monobromo derivative that forms is exposed to a bromine source and can further react giving a mixture of polybrominated derivatives, which is very difficult to purify.
It has now been found that the reaction of 2,6-dimethyl-benzoic acid (II) with sodium bromate and hydrobromic acid in the presence of light gives 2-bromomethyl-6-methyl benzoic acid (I) in high yield and purity.
In particular, the process of the invention provides the following advantages:
1. Bromine is generated in situ at low temperature and during the reaction the brominating agent is never present in an excess;
2. Compound (I) crystallizes out while compound (II) remains in solution, which strongly decreases polybromination.
According to the present invention, 2,6-dimethyl-benzoic acid is dissolved in an organic halogenated solvent, preferably selected from the group consisting of methylene chloride, dichloroethane, chloroform, more preferably methylene chloride, and added to a sodium bromate aqueous solution. The molar ratio of 2,6-dimethylbenzoic acid to sodium bromate ranges from 3:0.8 to 3:1.2 and is preferably 3:1.
The mixture is cooled down to 0-10xc2x0 C., preferably to 5xc2x0 C., then added with a solution of hydrobromic acid in equimolar amount in respect of 2,6-dimethyl benzoic acid and in the presence of light, preferably in the presence of a light source with a wavelength ranging from 200 to 750 nm. The exposure to the light is critical to obtain high yield and selectivity. Experiments performed in the dark failed.
2-Bromomethyl-6-methyl benzoic acid (I) crystallizes out from the mixture; this represents a further advantage of the present invention, because the product can be easily isolated by filtration without troublesome working up.
Compound (I) is usually obtained with high purity, i.e. free from 2,6-dibromomethyl benzoic acid. Small amounts of lactone (V) may be present, but this is not a drawback, since compound (I) is usually a synthon of compound (V) or of other products whose preparation involves ring opening of compound (V).
Compound (V) is typically obtained from compound (I) by treatment with equimolar amounts of an organic base selected from tertiary amines or weak inorganic bases, preferably N-ethyl-diisopropylamine or sodium bicarbonate.
Compound (I) can be conveniently used for the preparation of esters of general formula (III) 
wherein R represents
a straight or branched alkyl chain, preferably a C1-C4 straight or branched alkyl chain.
Compounds of formula (III) can be prepared, according to conventional methods well known to the skilled person, by reacting compound (I) or a reactive form thereof with an alcohol ROH wherein R is as defined above.
Preferred are compounds of formula (III) wherein R is methyl or ethyl (methyl- and ethyl-esters IIIa and IIIb), prepared via derivatisation of compound (I) with thionyl chloride in the presence of N,N-dimethyl formamide followed by solvolysis with methanol and ethanol, respectively.